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August 10, 2011 6:04 pm
A huge international study of multiple sclerosis has revealed 57 genetic variations that underlie the disease. The results prove that MS is primarily a disorder of the immune system, which then attacks the central nervous system.
For the study, published in the journal Nature, 250 researchers studied the differences in DNA between 9,800 people with MS and 17,400 healthy control subjects. They discovered 29 new genetic variants, besides confirming 26 mutations suspected previously from smaller studies.
“Our research settles a long-standing debate on what happens first in the complex sequence of events that leads to disability in MS,” said Alastair Compston, professor of neurology at the University of Cambridge. “It is now clear that MS is primarily an immunological disease, and this has important implications for future treatment strategies.”
MS is the most common disabling disease among young adults, affecting an estimated 100,000 people in the US and 2.5m worldwide. Like many complex disorders, it results from the interaction of a large number of genes and environmental factors; inheritance studies suggest that nature and nurture each contribute about 50 per cent to the risk of developing MS.
Most of the genes implicated in the latest MS study play pivotal roles in the workings of the immune system – particularly in the function of T-cells, which attack foreign substances in the body, and interleukins, natural molecules that facilitate interactions between immune cells.
About a third of the genes found to be involved in MS have already been implicated in other auto-immune disorders, such as rheumatoid arthritis, type-1 diabetes and Crohn’s disease, indicating that the same general processes can start a range of diseases with quite different symptoms.
There are now two big questions for understanding these diseases: first, what triggers the aberrant auto-immune response in the first place – possible causes range from viral infection to vitamin D deficiency – and second, what directs the damage to occur in particular tissues? In MS, the aberrant T-cells migrate from the blood into the brain and nervous system, where they induce the immune system to attack nerve fibres and their protective insulation, the myelin sheath.
The results of the study show that drugs to treat MS should focus on preventing the initial faulty immune response, Prof Compston said. One MS drug on the market (Tysabri, marketed by Biogen Idec and Elan) and three more in clinical development work in this way, although they sometimes have serious side-effects.
“We are now in the second phase of MS treatments, which are much more effective than the first phase – but much less safe,” he added. “We can now move on to a third phase where the drugs will be very effective and very safe.”
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